“Rare” Genetic Sequence Doesn’t Mean the COVID Virus Was Engineered

The theory that the COVID-19 pandemic was caused by the Sars-CoV-2 virus leak from the Wuhan Institute of Virology in China was recently revived after an explosive article in the Wall Street Journal (WSJ) the authors claimed “the most compelling reason to favor the lab leak hypothesis is firmly established in science.” But does the science really support the claim that the virus was developed in a lab?

By understanding the origin of a viral outbreak, scientists can gain important information about viral lines and steps can be taken to prevent similar outbreaks in the future. As such, the origin of Sars-CoV-2 has been debated since the start of the pandemic and remains an active topic of discussion among scientists.

It has long been known that viruses similar to the original Sars-CoV that causes Sars are found in bats. These viruses have been well studied in China, where the Sars outbreak originated in 2002. But related viruses have been found worldwide.

Unsurprisingly, coronaviruses are once again implicated in a pandemic, the third such event in the 21st century – first Sars, then Mers, now COVID-19. While a natural origin seems likely — and many have long warned of the danger posed by viruses circulating in the wild — scientists shouldn’t jump to conclusions.

One important way scientists can determine the origin of a virus is by looking at its genome. In the WSJ article, the authors, Prof. Richard Muller, an astrophysicist, and Dr. Steven Quay, physician and chief executive of Atossa Therapeutics, claim that Sars-CoV-2 has “genetic fingerprints” from a virus derived from a laboratory. They say that the presence of a certain genetic sequence (CGG-CGG) is a sign that the virus originated in a lab.

To understand the claims being made, we must first understand the genetic code. When a virus infects a cell, it hijacks the cellular machinery and instructs it (genome) to make more copies of itself. This genome is made up of a long string of molecules called nucleotides, each represented by the letters A, C, G, or U.

A group of three nucleotides (known as a codon) instructs a cell to make an amino acid, the most basic molecular building block of living things. Most amino acids are encoded by several codons. CGG is one of six possible codons that instruct the cell to add the amino acid arginine.

The authors of the WSJ article claim that Sars-CoV-2 originated in a lab based on the presence of a “CGG-CGG” sequence. They claim this is an “easily available and convenient” codon pair that scientists prefer to use to produce the amino acid arginine. But for anyone with knowledge of the techniques required for genetic engineering, this double-CGG is usually no more difficult or easier to produce than any other pair of codons encoding arginines.

No reason why CGG-CGG had to be made in the lab

The authors claim that the CGG codon is less common than the other five possible codons in betacoronaviruses (the family of coronaviruses to which Sars-CoV-2 belongs). Looking at related coronaviruses, the CGG codon encodes about 5% of all arginines in Sars-CoV, compared to about 3% of all arginines in Sars-CoV-2. Although CGG is less common than other codons, the authors’ argument provides no reason that the double CGG sequence could not exist naturally.

The authors state that recombination (when viruses infecting the same host share genetic material) was the most likely way for Sars-CoV-2 to obtain the double CGG sequence. They note that the double-CGG codon pair is not found in other members of this “class” of coronavirus, so natural recombination could not possibly generate a double-CGG. However, viruses do not rely solely on preassembled segments of genetic material to evolve and expand their host range.

The authors also claim that mutation (random copy errors) is unlikely to generate the duplicate CGG sequence. But viruses are evolving at a rapid pace, so much so that the accumulation of mutations is a common inconvenience of virology studies. Recombination is one way viruses evolve, but the authors’ rejection of mutation as a source of viral change is an inaccurate description of reality.

The latest claim that the first Sars-CoV-2 virus sequenced was ideally suited to the human host ignores evidence of viral circulation in local animal populations, animal-to-animal transmission, and the rapid evolution driving increasing transmissibility. of the newer variants. If the virus was ideally adapted to humans, why is there so much further evolution visible?

Disappointingly, many other media articles seem to have accepted and echoed the claims made in the WSJ piece. The origins of Sars-CoV-2 may remain unresolved, but no evidence has been presented in the WSJ piece that scientifically supports the concept of a lab leak of a genetically engineered virus.

Written by

Keith Grehan – Postdoctoral Researcher, Molecular Biology, University of Leeds Natalie Kingston – Researcher, Virology, University of Leeds

Originally published on The Conversation.